The metabolism of chromate by rat liver microsomes has been studied. Incubation of chromate with microsomes in the presence of the enzyme cofactor NADPH, resulted in reduction of chromate to chromium(III) and the formation of a Cr(III)-NADPH complex. In the absence of NADPH no reduction occurred. Only a small amount of chromate reduction was seen with NADPH in the absence of microsomes. Metyrapone inhibited the extent of chromate reduction by microsomes and NADPH. CaCr04 caused a slight induction of cytochrome P-450 when injected in rats (20 mg/kg) 16-19 hours before isolation of microsomes, however, Na2Cr2O7 and NiCO3 showed no such effect under the same conditions. Chromate showed no binding to calf thymus DNA in the absence of microsomes and NADPH. Significant binding of chromium to DNA was found when chromate was incubated with DNA in the presence of microsomes and NADPH. Chromium(III) may be the ultimate carcinogen of carcinogenic chromium compounds. Microsomes mediated the binding of nickel (NiCO3, Ni3S2, Ni2S4, NiO and NiS) to calf thymus DNA. Although binding occurred in the absence of microsomes, a greater (Ni)/(DNA-P) ratio was found when microsomes (in the absence or presence of NADPH) were present. Metabolism of metal carcinogens appears to be important in determining their effectiveness as carcinogens.